Abstract: Objective: To evaluate the correlation between the expression of CyclinD1, c-myc and p53 genes and the biological behavior of hepatocellular carcinoma (HCC). Methods: Immunohistochemical technology (EnVision^TM plus) was applied to detect the expression of CyclinD1, c-myc and p53 in 52 HCC tissues and their adjacent liver tissues. Results: The positive rates of CyclinD1 and c-myc were significantly higher in the HCC tissue than those of adjacent liver tissue (P<0.05). There was a positive correlation between the expression of p53 and CyclinD1 and c-myc in the HCC tissue (r=0.4637, P=0.0022, r=0.3445, P=0.0273, respectively). The positive rates of CyclinD1, c-myc and p53 in the HCC tissue were significantly correlated with the presence of extrahepatic metastasis, the recurrence of tumor and the differentiation of tumor (P<0.05). The positive rate of CyclinD1 was significantly correlated with the ortal vein tumor thrombus (P<0.05), The positive rate of p53 was significantly correlated with the level of serum alpha-fetoprotein (AFP) and tumor specific growth factor (TSGF) (P<0.05). The positive rates of CyclinD1, c-myc and p53 were not correlated with the clinical stage, the diameter of tumor, the number of tumor and the level of serum HBsAg. Conclusions: The over-expression of CyclinD1, c-myc and p53 proteins may contribute to the proliferation of hepatoma cell, improve the aggressive ability of hepatoma cell, and relates to the initiation and progression of HCC.